Myocarditis is an important cause of heart failure among adolescents and young adults. While about 33% of myocarditis patients recover, the remainder may develop chronic dilated cardiomyopathy which accounts for 25% of all heart failures in North America. Coxsackievirus B3 (CB3) infections have been implicated in around 40% of myocarditis cases. Antiviral drugs and immunosuppressive therapies have given mixed results, requiring further research in order to develop effective therapies. Studies of CB3-induced myocarditis in mice have provided valuable information about the role of the adaptive, acquired immune response to CB3 in the development of autoimmune myocarditis. Although the adaptive T cell response to CB3 is known to play a role in the development of myocarditis, little is understood on how the early, innate immune response to CB3 infection effects the development of autoimmune disease. The aim of this proposal is to characterize the innate immune response to CB3 infection in order to determine the factors that lead to autoimmune disease. We hypothesize that the early innate immune response to CB3 infection determines the later adaptive immune response leading to the development of autoimmune myocarditis. To investigate this hypothesis, we propose three specific aims: (i) to examine the role of early innate immune cytokines, (ii) the role of early innate immune cells, and (iii) the role of complement in the development of autoimmune myocarditis. The findings generated by these studies will aid in understanding the development of autoimmune disease initiated by infection.